Ro. Morgan et Mp. Fernandez, MOLECULAR PHYLOGENY OF ANNEXINS AND IDENTIFICATION OF A PRIMITIVE HOMOLOG IN GIARDIA-LAMBLIA, Molecular biology and evolution, 12(6), 1995, pp. 967-979
The homologous repeats of annexin tetrads are believed to have origina
ted by successive duplication and fusion from a putative monomeric pre
cursor, but neither the nature of their ancestor nor the events leadin
g to the formation of different subfamilies have been elucidated. We h
ave performed molecular phylogenetic analysis of aligned annexin nucle
otide and amino acid sequences to characterize subfamily branching, to
delineate the temporal order of appearance of individual repeat units
, and to gain insight into the origin and nature of the primordial uni
t. All extant annexins appear to have a common tetrad precursor that m
ay have originated from a progenitor unit resembling repeat 3, followe
d by the generation of repeats 4, 1, and 2 from a more evolved progeni
tor with subsequent fusion. Repeat sequences of the earliest human ann
exins VII and XIII were used to identify alpha-giardin genes as primit
ive homologues from the unicellular protozoan Giardia lamblia, which d
iverged from eukaryote lineage 1-1.5 billion yr ago. The significant h
omology between alpha-giardins and annexins suggested that the cell me
mbrane adhesive role of these proteins may be a common, fundamental pr
operty of the annexin C-terminal core region. Purported annexin VII of
Dictyostelium discoideum was reclassified as new annexin XIV, three C
aenorhabditis elegans genes were assigned to new subfamilies XV, XVI,
and XVII, and plant annexin XVIII from Medicago saliva was among the e
arliest diverging subfamilies. Annexins I and II were found to be clos
ely related, but analysis of protein mutation rates confirmed that the
former is evolving up to three times more rapidly. The inclusion of e
arly phyla in annexin taxonomy provides a useful basis for assessing t
he structural and functional changes associated with annexin evolution
.